Maintained by Robin Tecon, microbiologist and postdoctoral researcher at the Swiss Federal Institute of Technology Zürich. This blog is about bacteria (and other microbes) and the scientists who study them.

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Sunday, January 06, 2013

The new biology of Carl Woese

Carl Woese, one of the giants of contemporary biology,
passed away a day before New Year’s Eve (see the NY Times obituary). Woese, an
American microbiologist from the University of Illinois, revolutionized our
understanding of life with the discovery of a new domain of living organisms,
the Archaea, and the creation of a
universal tree of life made of three main branches (Bacteria, Archaea and Eukarya) (Woese, 1990). This discovery is already more
than thirty years old, but is not very well known to the general public,
to say the least… And now with Woese’s death the possibility of a Nobel
nomination vanishes.

Everything we do nowadays in microbiology labs is to some extent influenced by the work done by Woese in the seventies
and eighties. This is one reason why I entitled this post “The new biology of
Carl Woese”. The other reason is a 2004 article by Woese, “A new biology for anew century”, which offers a great perspective on our job and which contains some
juicy controversial elements. But let’s begin with the landmark contribution of
Woese to the field of biology.

Before the sixties and the advent of molecular phylogeny,
the classification of bacteria seemed an insoluble problem, since morphology
and metabolism were not good enough to allow us to order the
bacterial life forms. Woese, a physicist by training, decided in 1966 that he
could give it a try using the powerful tools of molecular biology. At that time
many researchers had turned towards proteins in order to build phylogenetic
trees, following the pioneer work of Linus Pauling on hemoglobin. Woese didn’t
follow the consensus and decided to use ribosomal RNA as source material.
Thanks to a tedious technique called oligonucleotide cataloging, he was able to
reconstruct the rRNA sequence and did that for about sixty bacteria. It took
ten years.

In 1976, Woese used his technique on methanogens, a diverse
group of microbes that nobody knew how to classify, and bingo! He had stumbled
on something that no one suspected: a new kind of living organisms, neither
bacteria nor eukaryotes, the Archaea.
He published his findings in PNAS (Woese & Fox, 1977), but the reception by
the scientific community was far from enthusiastic. The Nobel laureate Salvador
Luria told Woese’s colleague, Ralph Wolfe, that he should dissociate himself
from this “nonsense” in order to maintain his reputation. Ernst Mayr, the famous
evolutionist, also dismissed the idea of a third domain of life as nonsense,
and he kept this view until his death in 2005… (In a 2002 interview to Bioessays, Mayr said that “Only a non-biologist could have come up with this”.)
So did Lynn Margulis, as you can read in this previous post. As to those who were not openly opposed to Woese’s conclusions, they were
mostly silent. This initial backlash left profound wounds in Woese, even years
after the resistance had faded away. Today, the three domains of life
phylogeny has become textbook knowledge; in labs all around the world,
microbiologists use ribosomal RNA to characterize environmental isolates,
without bothering to culture the microbes in the first place! And a great
resource such as the Ribosomal Database Project would not exist but for Carl
Woese’s work. (I found most of the information above in a very interesting
article by Virginia Morell, published in Science in 1997.)

Interestingly, Woese’s work correlates with the development
of biotechnology, particularly high-throughput DNA sequencing, which led to the
human genome project and continues to unleash giant projects such as the human
microbiome. This is the science of entrepreneurs such as Craig
Venter, and certainly a far cry from the past. This powerful but
technique-oriented biology, however, left Woese unimpressed. In his article “A
new biology for a new century” (Woese, 2004), he wrote, p. 173:

“By the end of the 20th century, however, the molecular vision
of biology had in essence been realized; what it could see of the master plan
of the living world had been seen, leaving only the details to be filled in.
How else could one rationalize the strange claim by some of the world’s leading
molecular biologists (among others) that the human genome (a medically inspired
problem) is the “Holy Grail” of biology? What a stunning example of a biology
that operates from an engineering perspective, a biology that has no genuine
guiding vision!”

And he added, p.185: “Biology today is little more than an
engineering discipline.” The culprit, according to Woese, is the reductionism
that permeated biology throughout the 20th century. But what does
one mean precisely by reductionism? Woese distinguishes what he calls “empirical
reductionism” from “fundamentalist reductionism”. The former is nothing more
than the methodology that scientists follow (we are reductionist – one may say
analytical – because, you know, that works…). In contrast, “fundamentalist
reductionism” is a world view that asserts that knowing the constituents is
enough to know the whole, and this one Woese finds problematic. He wrote,
p.174: “It is impossible to discuss modern biology without the cacophony of
materialistic reductionism throughout.” This is an exciting claim, although I don’t
think it’s easy to separate the “empirical” from the “fundamentalist”
reductionism, and to say which one influenced most the development of biology.

Woese acknowledged that reductionism had helped to solve
important problems in biology, but he thought that it was time to move on:

“The molecularcup is now empty. The time has
come to replace the purely reductionist “eyes-down” molecular perspective with
a new and genuinely holistic, “eyes-up,” view of the living world, one whose
primary focus is on evolution, emergence, and biology’s innate complexity.”
(p.175)

Let’s be ambitious and tackle the big questions again!
Evolution, development, the origin of life, the complexity of interactions
between organisms, these are all topics that need to be explored further. This
is a heartening message, because it tells us that we are far from being done
with biology. (Woese compared the contemporary situation in biology with the
one of physics at the end of the 19th century: people claimed that
everything was known… Until it was turned upside down in the 20th
century. Woese believed the same thing may happen to biology in the 21th
century.) For Woese, one of these big questions is the evolution of the cell
(Woese, 2002). And indeed, this is one of the rare topics that hosts a true
controversy in the scientific community these days!

I tend to be skeptical when I read the word “holistic”,
because too often it means hollow concepts in disguise. But from someone like
Carl Woese, it is a different story. He did his share of “reductionist”
biology, so he knew what he was talking about. I also feel that nowadays
biology is not as exciting as it could be. We are making catalogs of
everything: catalogs of genes, of proteins, of genomes, of organisms… We need to remember that cataloging is not per
se a final goal of biology… We will see whether Woese’s vision of biology
unfolds in the 21th century!

Let’s give the final word to Woese, one of the greatest biologists
of our era:

“Our task now is to resynthesize biology; put the organism back
into its environment; connect it again to its evolutionary past; and let us
feel that complex flow that is organism, evolution, and environment united. The
time has come for biology to enter the nonlinear world.” (p.179)

6 comments:

I am glad that you chose the final quote that you did. All sequencing aside, it is vital to expand culturing abilities and to attempt to understand the vast roles of microorganisms in the environment. This was a great read.